Clear-Cell RCC: Impact of Risk Stratification and NCCN Guidelines on 1L Therapy
Key opinion leaders reflect on treatment approaches for renal cell carcinoma in light of factors like risk classification, symptom severity, and patient preferences, with considerations ranging from active surveillance to systemic combination therapies.
Summary:
In the context of renal cell carcinoma (RCC) treatment decisions, risk stratification plays a pivotal role. For patients with International mRCC (metastatic RCC) Database Consortium favorable-risk disease, the initiation of medication may not be immediately necessary. Active surveillance is a viable option, especially for those with slow-growing and asymptomatic disease, allowing delays in medication initiation for 1 to 3 years. Metastasis-directed treatment, involving surgery or radiation to specific sites, is also considered for patients with limited disease sites, further postponing the need for immediate medication.
For patients requiring medication, the choice between immunotherapy (IO) and tyrosine kinase inhibitor (TKI) combinations depends on factors such as disease severity and symptoms. IO-TKI combinations, like ipilimumab-nivolumab, are preferred for patients with severe symptoms and a need for rapid disease response. However, for patients with slow-growing disease and fewer symptoms, single-agent TKI therapy may be considered, particularly for those who wish to avoid immunotherapy initially. If initial TKI therapy proves ineffective, subsequent immunotherapy in the second line remains a viable option. Patients with intermediate and poor risk disease, characterized by shorter overall survival, may necessitate more aggressive treatment. Aggressive histological features, such as sarcomatoid histology, often indicate responsiveness to combination immunotherapy, specifically ipilimumab and nivolumab, offering potential long-term responses. Symptomatic patients in the intermediate and poor-risk setting may benefit from IO-TKI combinations due to their high response rates.
The interpretation and application of data in clinical practice involve assessing risk stratification, considering National Comprehensive Cancer Network (NCCN) guidelines, and incorporating clinical judgment. Patient values and goals of care are crucial considerations. The choice between IO-TKI combinations, such as lenvatinib and pembrolizumab, versus IO monotherapy or specific TKIs, like axitinib, depends on factors like disease burden, symptomatic presentation, and the desired treatment-free interval. Factors like TKI half-life and potential adverse effects further guide treatment decisions. Consideration of outcomes beyond survival, such as quality of life, becomes essential in treatment decisions. Trials like CheckMate 9ER and CheckMate 214 demonstrated improvements in quality of life for patients on IO-TKI combinations compared to sunitinib. Despite significant advances in RCC treatment, the importance of clinical trials in exploring new medications and combinations is emphasized as a means to further enhance patient outcomes.
Summary is AI-generated and reviewed by Cancer Network editorial staff.
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